macaque monkey brain

Additionally, axospinous, axosomatic, and axodendritic spine sizes appear to increase with age in the prefrontal cortex, and the extent of these structural changes in superficial cortical layers was significantly associated with performance measures on an object recognition task (36, 37). The 23 species of macaques inhabit ranges throughout Asia, North Africa, and Gibraltar. With respect specifically to brain aging research, it will be critical to objectively determine whether the advantages associated with the novel experimental tools that marmoset research can provide outweigh the potential disadvantages of reduced gyral complexity and increased phylogenetic distance from humans (102). “Theories of consciousness have suggested that central lateral thalamus plays a key role in keeping the cortex ‘awake.’ This study provides important evidence supporting that theory.”, Moreover, the paper “gives us new insights into the circuitry and brain dynamics that produce consciousness,” wrote Miller, who wasn’t involved with the new research. Shutterstock / Blueton. This article is a PNAS Direct Submission. Lewis, J.W., Van Essen, D.C.: Corticocortical connections of visual, sensorimotor, and multimodal processing areas in the parietal lobe of the macaque monkey. Recent public concern about nonhuman primate research has made it imperative to attempt to clearly articulate the potential benefits to human health that this model enables. Extracellular recordings across various hippocampal subfields have shown that neurons specifically in the CA3 region become hyperexcitable (higher firing rates) in older animals, whereas CA1 pyramidal cell firing rates are not different between adult and aged rats (17). In particular, the human audiogram to 60-dB tone stimuli ranges roughly from 31 Hz to 17.6 kHz, and macaques show an acoustic range between 28 Hz and 34.5 kHz when given tones of the same intensity (71). CRISPR-Cas9 gene editing can improve the effectiveness of spermatogonial stem cell transplantation in mice and livestock, a study finds. (F) Frontal radiation FA was also not associated with ABR thresholds. One study was able to bridge the gap between these cellular data in aged rats and imaging data from older humans by combining ensemble electrophysiological recordings with cell type-specific imaging in the medial temporal lobe of cognitively assessed aging rhesus macaques (27). 3 B–D). Non-human primates, especially macaque monkeys, with close phylogenetic relationship to humans, are highly valuable and widely used animal models for human neuroscience studies. More recently, the impact that hearing loss, in particular, has on cognition has reemerged as a topic of research interest. Lesion and functional imaging studies in humans indicate that the integrity of medial temporal lobe brain structures, including the hippocampus, is critical for episodic memory formation (13, 14). The present review will highlight how nonhuman primates provide a critical bridge between experiments conducted in rodents and development of therapeutics for humans. One location along the ascending auditory pathway where these interspecies differences are clear is within the superior olivary complex (SOC) in the ventral brainstem. Image credit: Shutterstock/greenbutterfly. During the experiments, for example, a clinical anesthesiologist was to present to make sure the monkeys “received the same level of care as human patients in the hospital,” said Redinbaugh, and the animals were monitored both during and after the experiments to “ensure their health and wellbeing,” among other measures, she said. A critical aspect of the experiment was to correctly evaluate wakefulness in the two monkeys used in the experiment, dubbed Monkey R and Monkey W. “We modeled our assessment of wakefulness in monkeys on clinical measures that are used to assess coma patients or patients that are undergoing anesthesia,” Redinbaugh told Gizmodo. Face recognition and the interpretation of facial expressions and gaze direction play a key role in guiding the social behavior of human beings, and new study results point to similar mechanisms in macaques. 105 (Springer Nature: The Mammalian Auditory Pathway: Neuroanatomy, Copyright 1992). Comparison of human, macaque, and mouse brains. 2017-10: New 3d viewer: in addition to the wholebrain surface viewer, a per-region mesh viewer is under way. Because the impact that age will have on a specific neural network cannot necessarily be predicted a priori, it is essential to examine regions independently as age-related changes in one circuit may not generalize to those observed in another. “Essentially, we were looking for increases in behaviors that you would normally see in an animal—or human—that was waking up from anesthesia.”. Anatomical studies in aging macaques have provided substantial evidence that the total number of neurons in the prefrontal cortex (28⇓–30) and medial temporal lobe (31⇓–33) does not change across the lifespan in the absence of neurodegenerative disease. Although the evidence is still limited, a growing body of research suggests music may have beneficial effects for diseases such as Parkinson’s. Other studies conducted in the rat hippocampus suggest that a neuronal change that may contribute to this is altered calcium homeostasis in older neurons (18). is a guest editor invited by the Editorial Board. Finally, another possibility is that the extent of neuronal connectivity between regions may determine the degree to which brain functions covary across the lifespan through mechanisms associated with hyperexcitability or changes in synaptic function. Several studies discussed here exemplify how nonhuman primate research has enriched our understanding of cognitive and sensory decline in the aging brain, as well as how this work has been important for translating mechanistic implications derived from experiments conducted in rodents to human brain aging research. 104. The older animals were shown to be significantly impaired relative to the younger animals (Fig. (E) Frontal radiation FA was not associated with auditory processing. Furthermore, given the rich literature base on cognitive and sensory aging in the macaque that does not yet exist in the marmoset, combined with major advances in fast gene-editing technologies such as the CRISPR/Cas9 system (103), a parallel approach may be to expand the suite of tools available in the marmoset to macaques in order to take advantage of these past advances. Reproduced with permission from ref. Together, these observations indicate that auditory processing abilities functionally covary specifically with aspects of cognition driven by medial temporal lobe networks, regardless of auditory acuity. Image credit: Acacia Dishman/Medical College of Wisconsin. Interaural time differences are the primary cue used to localize lower frequency sounds, and these computations primarily involve the medial superior olivary (MSO) nucleus (74, 75). This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. 5B) and lower acoustic thresholds (Fig. The scientists also monitored their EEG responses to both common and unusual sounds, “which can distinguish consciousness from unconscious subjects,” she added. (A) Images of the dorsal surface of a human brain, macaque brain, and mouse brain. Three rhesus macaques (1 male, 2 females, 4–6 kg, 8–9 years of age) were tested. The basic laminar organization of excitatory local circuitry in the primary visual cortex of the macaque monkey is similar to that described previously in the cat's visual cortex . Leslie G. Ungerleider, NIMH-NIH "This is an extraordinarily detailed and comprehensive atlas of the macaque monkey brain. 2018-06: Visualize your own data inside a brain atlas with SBA Composer. Macaques with object recognition memory deficits display hyperactivity in the CA3 region of the hippocampus that is associated with fewer somatostatin(SOM)-positive inhibitory interneurons. One often misunderstood aspect of the normative brain aging process is that while an enormous absolute number of individuals present with a dementing neurodegenerative disease at some time in their life (14% of people over the age of 70 y), the vast majority of people (86%) take healthier cognitive trajectories (2). Together, these findings suggest that age-associated changes in hippocampal inhibitory circuits may lead to CA3 hyperexcitability and circuit dysfunction that impacts memory. We showed that the TG monkeys carrying the huMCPH1 transgene did not manifest an enlarged brain size, implying that a single gene likely has a limited effect on neural progenitor pool proliferation during brain development. Because cognitive problems arise relatively late in the progression of these diseases, some participants considered to be aging normally may actually have undetected pathophysiological brain markers during the period when behavioral testing is conducted (5). During the experiment, the scientists attempted to stimulate various parts of the deep brain, but none elicited the same response as the central lateral thalamus, which emerged a kind of consciousness hotspot in the brain. New research published today in Neuron takes us a small but important step closer to the answer. 58. George is a senior staff reporter at Gizmodo. 2B). Conversely, the domestic mouse cannot hear 60-dB tones below 2.3 kHz and can hear up to 85.5 kHz (71). Macaques are principally frugivorous, although their diet also includes seeds, leaves, flowers, and tree bark. Despite evidence dating back several decades to suggest that individuals with poorer sensory function are more likely to have cognitive problems later in life, the neurobiological processes responsible for these associations have not been a subject of intense research (79⇓⇓–82). ), suggesting that RRRs are conserved among mammalian species. (B) Boxplots of pyramidal neuron baseline firing rates recorded from the perirhinal cortex (PRC) and CA3 in adult and aged monkeys. Macaque brain. What that in mind, the new research could result in effective new therapies to treat disorders of consciousness, improved deep brain stimulation as a surgical technique, and better drugs for anesthesia. 5C). Animals. First, it might be the case that embryological and developmental differences between the frontal and temporal lobes predispose each region to succumb to distinct risk factors associated with brain aging. Macaque monkeys have become the predominant nonhuman primate model system in brain aging research due to their striking similarities to humans in their behavioral capacities, sensory processing abilities, and brain architecture. Knowing how it makes people unconscious is an important step in making anesthesia safer.”. (Top) Human SOC is characterized by a relatively small LSO nucleus (light blue) and an elongated MSO nucleus that is surrounded by other olivary nuclei (gray). This observation highlights a major challenge in cognitive aging research of understanding each individual’s unique behavioral and neurobiological profile. Because MCPH1 is a key gene for neurogenesis, one of the expected phenotypic outcomes in the transgenic monkeys would be a larger brain, which was not the case in this study. Baseline firing rates were significantly higher in the CA3 region, but not in the perirhinal cortex, of the older monkeys compared with the adults, consistent with the regional specificity of the age-associated hyperactivity observed in aged humans (Fig. Nonhuman primates provide the animal model that is closest to humans and remain an important bridge for testing the veracity of discoveries effective in rodents when clinical applications of these are being considered for human testing. From February 2001 through May 2019 colloquia were supported by a generous gift from The Dame Jillian and Dr. Arthur M. Sackler Foundation for the Arts, Sciences, & Humanities, in memory of Dame Sackler's husband, Arthur M. Sackler. Electrophysiological evidence from studies utilizing in vitro slice preparations further indicate that frontal cortical and medial temporal lobe networks are differentially impacted by normative aging. Notice the striking differences in the size and convolution complexity of the cerebral cortex across the 3 species. The brain remains the most mysterious organ in the human body. “This study puts thalamus back to the picture,” Aru, who is not affiliated with the new study, told Gizmodo. Examining the relationship between auditory function and cognitive decline in aging macaque monkeys, PhD dissertation, The University of Arizona, Tucson, AZ (2019). Health 3 December 2020 By Michael Le Page. E.A.B. Macaque monkeys, in particular, have been the predominant nonhuman primate model in neuroscience, although relatively recent advances in transgenic technologies for use in marmosets (99⇓–101) have rapidly established this anthropoid as a promising additional nonhuman primate tool. Baseline firing rates were significantly greater in the CA3 of aged animals relative to the adults. This would be fantastic if it led to advances in the areas of insomnia and narcolepsy. In this study, we use the intricate connections of frontal, cingulate, and parietal areas, well established by the anatomical literature, to derive a symmetrical histological connectivity matrix composed of 59 cortical areas. When this happened, the primates behaved just as they would when awake. This paper results from the Arthur M. Sackler Colloquium of the National Academy of Sciences, “Using Monkey Models to Understand and Develop Treatments for Human Brain Disorders,” held January 7–8, 2019, at the Arnold and Mabel Beckman Center of the National Academies of Sciences and Engineering in Irvine, CA. (C) Similarly, animals with higher right hemisphere fimbria-fornix FA had lower auditory brainstem response (ABR) thresholds. NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. Shapeshifting designs could have wide-ranging pharmaceutical and biomedical applications in coming years. Currently, most frameworks for understanding function in aging brains consider different cognitive and sensory operations in isolation from one another rather than taking into consideration the fact that different brains systems interact and influence each other’s functioning. We thank Michelle Albert for assistance with the graphics. The calcium hypothesis suggests that rebalancing intracellular calcium levels, and perhaps hyperexcitability, by increasing inhibition to control excess neural activity may rebalance circuit activity and help preserve memory function in aging. Based on acoustic sensitivity, the auditory system of mice should utilize calculations of interaural intensity differences in the LSO more so than the primate auditory system, which should utilize interaural time difference calculations in the MSO to a greater extent. Anatomical differences like these highlight the fact that sensory systems develop to process species-relevant information, and that differences in sensory transduction ranges will be reflected in the basic structure of an animal’s nervous system. Advances in medicine, education, and nutrition over the past century have decreased mortality rates in populations across the globe, resulting in longer average life expectancies (1). In particular, this review will highlight studies that have utilized aged macaques to gain network-level and regional insights into age-related episodic memory decline and hearing loss, which are 2 of the most commonly experienced alterations in brain function experienced by older individuals. (E) CA3 SOM neuron density and CA3 firing rates showed weak associations with object recognition performance. Adapted by permission from ref. The anterior insular cortex is a small brain region that plays a crucial role in human self-awareness and in related neuropsychiatric disorders. Nonhuman animals also do not spontaneously develop dementing neurodegenerative diseases, which eliminates a major confound often encountered in human brain aging research. NAS colloquia began in 1991 and have been published in PNAS since 1995. In neuroimaging analysis of macaques, brain extraction or skull stripping of magnetic resonance imaging (MRI) is a crucial step for following processing. The same monkeys underwent electrophysiological assessments of auditory thresholds, auditory system temporal information processing, and visual system temporal information processing. Macaque Monkey is a YouTube channel that upload everyday about MONKEY. This is largely due to evidence from large longitudinal studies that individuals with poorer acoustic function are at a higher risk of developing age-related cognitive decline and dementia (83, 84). The SOC is the first site of binaural integration in the auditory system, and is critical in computing the interaural time, intensity, and phase differences necessary for sound source localization in azimuth (72, 73). Older monkeys were impaired relative to adults on some, but not all, of the cognitive functions tested in the battery, indicating that distinct aspects of cognition operate partially independent of one another in aged macaques, as is the case in older humans (91⇓⇓⇓–95). The goal of this review is to begin to articulate the reasons that these research animals are a critical component of the experimental enterprise aimed at understanding the process of brain aging and to our quest to discover treatments that optimize brain and cognitive health. Finally, animal models help control for generational effects that sometimes influence human aging research (6) since young and aged animals can be exposed to similar testing and living conditions over the course of their lifespans. First, monkeys possess cognitive and sensory repertoires that more closely resemble those of humans compared with other animal models (7). 1). Rare neurons discovered in monkey brains. Understanding the primate brain at a similar level of detail is facilitated by optogenetics in the macaque monkey—a model organism with a brain structure similar to humans that can be trained to perform complex behavioral tasks. Human neuroimaging has revealed a specific network of brain regions—the default-mode network (DMN)—that reduces its activity during goal-directed behavior. In rodents, there are contradicting reports as to whether CaBP density increases or decreases with age; however, every study in the macaque has reported age-associated increases in the number of auditory neurons expressing these proteins (Fig. Nonhuman primates, in particular, have been central and arguably irreplaceable to cognitive aging research due to several critical features unique to these animals. Based on previous lesion studies in macaques, the 3 tasks associated with auditory processing all require the integrity of medial temporal lobe brain structures, whereas the tasks in this battery that require frontal and occipital cortex integrity were not associated with auditory processing. For example, intracellular recordings indicate that pyramidal neurons in the lateral prefrontal cortex become more excitable with age, as reflected by increases in membrane input resistance and action potential discharge to a given stimulation intensity (41). 58; and 59, which is published under CC BY 3.0. To that end, Redinbaugh, along with senior author Yuri Saalmann and their colleagues, devised an experiment with the intent of inducing consciousness in anesthetized subjects. (A) Representative probability map of the right hemisphere fimbria-fornix overlaid upon T1-weighted MRI (Top) and a fractional anisotropy (FA) map pseudocolored in copper (Bottom). The authors declare no conflict of interest. PRC firing rates were not different between age groups. Furthermore, these electrophysiological changes were significantly associated with performance on an object recognition task (41). The results discussed here call for a shift in focus in cognitive aging research toward understanding how different brain functions impact one another across a lifespan. The June 2018 release is out. Over the past several decades, neuroscientists have teased apart the various regions and networks in the brain to better understand how they contribute to normal cognitive function, but huge questions remain about consciousness and which parts of the brain can be described as the neural correlates of consciousness (NCCs)—that is, the specific brain regions that allow us to experience the smell of burnt toast, the redness of a blooming rose, or the richness of our internal thoughts. Max Planck scientists discover brain cells in monkeys that may be linked to self-awareness and empathy in humans. 3A). (A) Proportion of correct responses made by adult and aged rhesus macaques performing a delayed nonmatching-to-sample task at different delays. It can be used as 486 coronal, 346 horizontal, or 191 parasagittal 150-um thick 'sections'. (B) Animals with higher right hemisphere fimbria-fornix FA had better auditory processing abilities. Superior auditory processing, however, was related to better overall cognitive function. Author contributions: D.T.G. “I hope many studies will follow that will try to better understand the role of thalamus not only in the state of consciousness, but also in perceptual processes.”. Episodic memory refers to an individual’s recollection of a particular event in place and time and is considered among the most advanced forms of human memory. A major goal within the field of the neuroscience of aging is to determine what factors allow certain individuals to evade neurodegenerative disease, while others succumb to them. This circuitry is described here in the context of a two-level model that distinguishes between feedforward and feedback connections. By experimenting on macaque monkeys, researchers from the University of Wisconsin-Madison have uncovered new evidence affirming the central lateral thalamus as an NCC. Thus, the striking specificity by which anatomical connectivity, auditory physiology, and cognitive outcome measures covaried across the lifespan in this study indicates that normative aging impacts neural networks contained within the temporal lobe more similarly than circuits residing in other brain regions (i.e., between the frontal and temporal lobes in this study). A consistent finding from this work is that decreases in inhibitory neurotransmission at the level of the auditory brainstem (48⇓–50), midbrain (50⇓⇓–53), thalamus (50, 54, 55), and cortex (50, 56, 57) result in both hyperexcitability and changes in the tuning properties of central auditory neurons. Together, these data indicate that chemical expression patterns of CaBPs in the central auditory system are associated with peripheral auditory dysfunction. One important translational implication of this work is the suggestion that age-related episodic memory decline may be alleviated by manipulating the function of specific interneuron subtypes to rebalance local network activity. The brains were extracted and … and C.A.B. 2018-05: After 9 years of operation, ran broken link detector on the Scalable Brain Atlas ecosystem and fixed 40 issues. Animals with greater hippocampus-associated white matter integrity have better auditory processing capacities and lower auditory thresholds. Delay condition and Gibraltar right hemisphere fimbria-fornix FA had lower auditory brainstem with monkeys and humans this. Surface viewer, a per-region mesh viewer is under way shown to significantly... To self-awareness and empathy in humans occur within the central lateral thalamus as an NCC ) occur. Changes were significantly greater in the activity of circuits within the hippocampus that negatively impacts mnemonic processing rhesus macaque Macaca. 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